Endovascular sonothrombolysis has gained significant attention due to its benefits, including direct targeting of the thrombus with sonication and reduced side effects. However, the small aperture of endovascular transducers restricts the improvement of their potential clinical efficiency due to inefficient acoustic radiation. Hence, in an earlier study, we used vortex ultrasound with an endovascular ultrasound transducer to induce shear stress and enhance the clot lysis. In this study, the vortex acoustic transduction mechanism was investigated using numerical simulations and hydrophone tests. Following this characterization, we demonstrated the performance of the vortex ultrasound transducer in thrombolysis of retracted clots in in vitro tests. The test results indicated that the maximum lysis rates were 79.0% and 32.2% with the vortex ultrasound for unretracted and retracted clots, respectively. The vortex ultrasound enhanced the efficiency of the thrombolysis by approximately 49%, both for retracted and unretracted clots, compared with the typical non-vortex ultrasound technique. Therefore, the use of endovascular vortex ultrasound holds promise as a potential clinical option for the thrombolysis of retracted clots.
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Acoustic metasurfaces are two-dimensional materials that impart non-trivial amplitude and phase shifts on incident acoustic waves at a predetermined frequency. While acoustic metasurfaces enable extraordinary wavefront engineering capabilities, they are not developed well enough to independently control the amplitude and phase of reflected and transmitted acoustic waves simultaneously, which are governed by their geometry. We aim to solve the inverse design problem of finding a geometry to achieve a specified set of acoustic properties. The geometry is modeled by discretizing the continuous space into a finite number of elements, where each element can either be filled with air or solid material. Full wave simulations are performed to obtain the acoustic properties for a given geometry. It is computationally infeasible to simulate all geometries. To address this challenge, we develop an experimental design-based algorithm to efficiently perform the simulations. The algorithm starts with a few geometries and adaptively adds geometries to the set, such that they fill the entire space of the desired acoustic properties using a small fraction of the possible geometries. We find that the geometry needs to have at least 7 × 7 elements to obtain any given acoustic property with a tolerance of 5.4% of its maximum range. This is achieved by simulating 24 000 geometries using the proposed algorithm, which is only [Formula: see text] of the 563 × 10 12 possible geometries. The method provides a general solution to the inverse design problem that can be extended to control more acoustic properties.more » « less
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Perfluorocarbon nanodroplets (PFCnDs) are ultrasound contrast agents that phase-transition from liquid nanodroplets to gas microbubbles when activated by laser irradiation or insonated with an ultrasound pulse. The dynamics of PFCnDs can vary drastically depending on the nanodroplet composition, including the lipid shell properties. In this paper, we investigate the effect of varying the ratio of PEGylated to non-PEGylated phospholipids in the outer shell of PFCnDs on the acoustic nanodroplet vaporization (liquid to gas phase transition) and inertial cavitation (rapid collapse of the vaporized nanodroplets) dynamics in vitro when insonated with focused ultrasound. Nanodroplets with a high concentration of PEGylated lipids had larger diameters and exhibited greater variance in size distribution compared to nanodroplets with lower proportions of PEGylated lipids in the lipid shell. PFCnDs with a lipid shell composed of 50:50 PEGylated to non-PEGylated lipids yielded the highest B-mode image intensity and duration, as well as the greatest pressure difference between acoustic droplet vaporization onset and inertial cavitation onset. We demonstrate that slight changes in lipid shell composition of PFCnDs can significantly impact droplet phase transitioning and inertial cavitation dynamics. These findings can help guide researchers to fabricate PFCnDs with optimized compositions for their specific applications.more » « less
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This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis (CVST). This is a topic of substantial importance since current treatment modalities for CVST still fail in as many as 20% to 40% of the cases, and the incidence of CVST has increased since the outbreak of the coronavirus disease 2019 pandemic. Compared with conventional anticoagulant or thrombolytic drugs, sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves. However, previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes (e.g., recanalization within 30 min) in treating large, completely occluded veins or arteries. Here, we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wave-matter interaction-induced shear stress to enhance the lytic rate substantially. Our in vitro experiment showed that the lytic rate was increased by at least 64.3% compared with the nonvortex endovascular ultrasound treatment. A 3.1-g, 7.5-cm-long, completely occluded in vitro 3-dimensional model of acute CVST was fully recanalized within 8 min with a record-high lytic rate of 237.5 mg/min for acute bovine clot in vitro. Furthermore, we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo canine veins. This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies.more » « less
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null (Ed.)Bluetooth requires device pairing to ensure security in data transmission, encumbering a number of ad-hoc, transactional interactions that require both ease-of-use and "good enough" security: e.g., sharing contact information or secure links to people nearby. We introduce Bit Whisperer, an ad-hoc short-range wireless communication system that enables "walk up and share'" data transmissions with "good enough" security. Bit Whisperer transmits data to proximate devices co-located on a solid surface through high frequency, inaudible acoustic signals. The physical surface has two benefits: it limits communication range since sound travels more robustly on a flat solid surface than air; and, it makes the domain of communication visible, helping users identify exactly with whom they are sharing data without prior pairing. Through a series of technical evaluations, we demonstrate that Bit Whisperer is robust for common use-cases and secure against likely threats. We also implement three example applications to demonstrate the utility of Whisperer: 1-to-1 local contact sharing, 1-to-N private link sharing to open a secure group chat, and 1-to-N local device authentication.more » « less
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Abstract A promising new field of genetically encoded ultrasound contrast agents in the form of gas vesicles has recently emerged, which could extend the specificity of medical ultrasound imaging. However, given the delicate genetic nature of how these genes are integrated and expressed, current methods of producing gas vesicle‐expressing mammalian cell lines requires significant cell processing time to establish a clonal/polyclonal line that robustly expresses the gas vesicles sufficiently enough for ultrasound contrast. Here, we describe an inducible and drug‐selectable acoustic reporter gene system that can enable gas vesicle expression in mammalian cell lines, which we demonstrate using HEK293T cells. Our drug‐selectable construct design increases the stability and proportion of cells that successfully integrate all plasmids into their genome, thus reducing the amount of cell processing time required. Additionally, we demonstrate that our drug‐selectable strategy forgoes the need for single‐cell cloning and fluorescence‐activated cell sorting, and that a drug‐selected mixed population is sufficient to generate robust ultrasound contrast. Successful gas vesicle expression was optically and ultrasonically verified, with cells expressing gas vesicles exhibiting an 80% greater signal‐to‐noise ratio compared to negative controls and a 500% greater signal‐to‐noise ratio compared to wild‐type HEK293T cells. This technology presents a new reporter gene paradigm by which ultrasound can be harnessed to visualize specific cell types for applications including cellular reporting and cell therapies.
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Active acoustic metamaterials incorporate electric circuit elements that input energy into an otherwise passive medium to aptly modulate the effective material properties. Here, we propose an active acoustic metamaterial with Willis coupling to drastically extend the tunability of the effective density and bulk modulus with the accessible parameter range enlarged by at least two orders of magnitude compared to that of a non-Willis metamaterial. Traditional active metamaterial designs are based on local resonances without considering the Willis coupling that limit their accessible effective material parameter range. Our design adopts a unit cell structure with two sensor-transducer pairs coupling the acoustic response on both sides of the metamaterial by detecting incident waves and driving active signals asymmetrically superimposed onto the passive response of the material. The Willis coupling results from feedback control circuits with unequal gains. These asymmetric feedback control circuits use Willis coupling to expand the accessible range of the effective density and bulk modulus of the metamaterial. The extreme effective material parameters realizable by the metamaterials will remarkably broaden their applications in biomedical imaging, noise control, and transformation acoustics-based cloaking.